Development of 3D printed grafts based on bone extracellular matrix (ECM) for bone regeneration

Bone is a dynamic tissue with the ability to heal and repair without scaring. Nevertheless, in cases of delayed recovery or large non-healing bone defects resulting from trauma, tumor, or infection, bone grafting is required1. The extracellular matrix (ECM) naturally provides cells with a supportive framework of structural as well as functional proteins, carbohydrates, and signaling molecules2. Furthermore, the ECM was proved to have an important role in successful bone healing, as it increases the interactions among osteoprogenitor cells and growth factors.

The overall goal of the proposed research was, therefore, to reveal the potential of bone ECM (bECM) as a bioactive material for the bioengineering of advanced bone grafts. To this end, ECM was isolated from porcine and human bones, and their distinctive properties were studied, revealing high similarities between the human and the porcine bECM, and indicating the high potential of porcine bECM for bone grafting. Furthermore, in vitro and in vivo biocompatibility studies showed no indication for an immunological response.

To address the technological aspects of graft additive manufacturing, we first developed a reproducible ECM bio-ink that can be thermally gelled and further crosslinked using natural crosslinkers. Next, we investigated the technological feasibility of 3D-bioprinting complex pbECM scaffolds by addressing the effect of different biomaterial properties and system parameters on the process and its outcomes. In addition, we studied the incorporation of osteogenic factors such as BMP-2 in the scaffolds for the enhancement of clinical efficacy and osteogenic properties.

To conclude, we have established the scientific as well as the technological basis for the development of novel 3D-printed pbECM-bone grafts and demonstrated their great potential use for bone regeneration.

1. Sutherland, D.; Bostrom, M. Grafts and Bone Graft Substitutes. 133–156.

2. Badylak SF, Freytes DO, Gilbert TW. Reprint of: Extracellular matrix as a biological scaffold material: Structure and function. Acta Biomater. 2015;23 Suppl(S):S17-26.